Head circumference (HC) is an important clinical parameter in neuropediatrics, but it is often missing or outdated in referral information. This can lead to subjective, reader-dependent estimation during MRI interpretation. We first aimed to compare magnetic resonance imaging (MRI)-based methods for HC measurement against the tape measure (ground truth), and second to establish an automated alternative. In 23 children (mean age 4.5 years, range 0.5-17 years), HC was prospectively measured with a tape measure (ground truth) on the day of MRI. MRI-based HC measurements were derived from 3D T1-weighted MPRAGE and followed a two-step workflow: measurement plane selection and circumference measurement within that plane. Plane selection was performed using visual-based, rule-based, atlas-based [(infant) FreeSurfer], or neural network (nn)-based methods. Circumference measurement was performed using manual ellipsoid, manual contour, automated ellipsoid, or automated contour methods. The relative technical error of measurement (r-TEM; acceptable < 1.5%) and intraclass correlation coefficient (ICC; two-way mixed ANOVA model) were used to assess accuracy and consistency with the tape measure. Visual-based with manual ellipsoid/contour and rule-based with manual ellipsoid/contour showed acceptable accuracy (r-TEM 0.73%-1.12%). Visual-based with automated ellipsoid and rule-based with automated ellipsoid also demonstrated acceptable accuracy (r-TEM 0.77% and 0.68%). Atlas-based with automated ellipsoid achieved the lowest r-TEM (0.55%), followed by nn-based with automated ellipsoid (r-TEM 0.75%). In contrast, automated contour approaches showed unacceptable accuracy (r-TEM 3.42%-4.21%). Seven nn-based measurements with automated ellipsoid/contour were spurious. ICCs were high across all methods (0.993-0.997); however, manual contour and automated ellipsoid were associated with overfitting issues. The developed, fully automated algorithm based on (infant) FreeSurfer provides precise and reliable head circumference measurements from pediatric MRI scans with acceptable overall accuracy and excellent consistency with manual measurements using a tape (gold standard). Our algorithm simplifies the head circumference measurement process and provides a reproducible, reader-independent value that enhances the interpretation of neuroradiological findings. Further studies should be conducted to validate with larger sample sizes and to develop deep neural network algorithms for segmentation.
Even though digital media use in early childhood has increased, compliance estimates vary depending on the screen time guideline applied. This study compared Portuguese, World Health Organization, and American Academy of Pediatrics recommendations within the same population, and examined factors associated with exceeding age-specific limits. Baseline data from 940 children aged two to six years (mean 4.67 ± 1.03; 52.8% boys) were analyzed. The mean daily screen time was 126 minutes. The exceedance prevalence and severity were classified according to each framework. Most children exceeded recommendations across all systems, with highest prevalence and severity under the Portuguese Society of Neuropediatrics, followed by the American Academy of Pediatrics and the World Health Organization. Despite systematic reclassification across guidelines, consistent determinants emerged: earlier age at first exposure (ORs ranging between 0.93 - 0.98), child Internet use (non-use: ORs between 0.06 - 0.38), higher maternal screen time (ORs between 1.02 - 1.04), and bedroom device access (ORs between 0.17 - 0.50) were associated with higher odds of exceeding limits. Parental awareness of recommendations was generally high, but quantitative restrictions were less consistently implemented. The findings suggest that prevalence estimates strongly depend on the guideline framework applied, while family-level determinants of excessive exposure remain stable across classification systems.
Diseases during childhood and adolescence such as cancer or attention-deficit/hyperactivity disorder (ADHD) can have an impact on brain development and place children and adolescents at increased risk for cognitive long-term problems. Most cognitive trainings currently available have limited efficacy and show limited transfer to nontrained tasks and everyday functioning. We developed a novel intervention (Mio-Training) aiming to increase metacognitive abilities at the intersection between exercise psychology and cognitive science to strengthen the cognitive development of pediatric patients with atypical brain development in the long term. The study assesses the efficacy of the Mio-Training on the primary (metacognitive abilities) and secondary outcomes (executive functions, processing speed, and memory) before the training, immediately after the training, and at a 3-month follow-up in patients with atypical development and healthy controls. The Mio-Training stimulates metacognition through 38 digital games, which playfully teach mnemonic strategies (ie, rehearsal, chaining, and associations), present intensive verbal and visual working memory training, and motor coordination tasks. The training group will train for 5 weeks, 3 times per week, for 20 minutes. The waiting control group will receive the training after completion of the study procedure. We will evaluate the efficacy of the Mio-Training on metacognitive abilities and cognitive performance in a randomized controlled clinical trial. We expect a long-term increase in metacognitive abilities associated with an increase in subjective and objective cognitive performance. The efficacy of the Mio-Training will be investigated in 3 subgroups (patients with cancer, ADHD, and healthy controls; each group n=40; all aged 8-16 years) using pre-intervention and post-intervention assessments. All participants will be randomly assigned to the Mio-Training or the waiting control group, stratified by age and sex. This study protocol describes the study design of the randomized controlled trial evaluating the efficacy of the Mio-Training. The project is funded from October 2024 to December 2027. Recruitment for healthy controls has been completed (n=40; October 2024-August 2025), recruitment for childhood cancer survivors (n=10, 25% participants recruited) is scheduled from August 2025 to December 2027, and recruitment for participants with ADHD (n=39, 97.5% recruited) is scheduled from October 2025 to September 2026. Data analyses have not yet commenced; first results from the ADHD subgroup are expected in early 2027, with findings from the cancer survivor subgroup anticipated in early 2028 following completion of recruitment. To strengthen cognitive development in young patients with atypical development, it is necessary to address the current lack of effective treatment options. The combination of cognitive and motor training with metacognitive abilities may support patients' cognitive maturation trajectories and will enable transfer of the training effect to everyday and school situations.
Cystic echinococcosis (CE) is a parasitic disease that commonly affects the liver and lungs. Orbital involvement is an unusual presentation, particularly in non-endemic areas, and poses diagnostic and therapeutic challenges. We report the case of a five-year-old girl from Syria who presented with orbital swelling and was ultimately diagnosed with disseminated CE. The diagnosis was delayed, and management was complicated by intraoperative cyst rupture and spillage. Surgical resection combined with antiparasitic therapy resulted in regression of the cysts. A scoping review of the literature identified 15 reports of orbital CE in children, most of them from endemic countries. CE should be considered in children presenting with cystic lesions and a history of migration from endemic areas. Early involvement of a CE reference center is essential to prevent complications and to optimize management.
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Comparative studies in paediatric-onset multiple sclerosis (PoMS) that also include highly effective monoclonal antibody therapies are rare. To compare treatment persistence, as a proxy of effectiveness and tolerability, across disease-modifying therapies (DMTs). Nationwide cohort study using Swedish MS Registry data on individuals with MS onset before age 18 from 2000 to 2024. Treatment persistence was analysed using Kaplan-Meier and Cox models, adjusted for demographics and treatment epoch. We included 383 individuals (69.2% female; median onset age 15.8 and 17.2 years at first DMT start), observed for a median 10.1 years (interquartile range (IQR): 5.5-15.5), yielding 934 treatment episodes: rituximab (272), injectables (263), natalizumab (248), fingolimod (86) and dimethyl fumarate (65). Median age at any treatment initiation, regardless of treatment sequence, was 18.9 years, with a median Expanded Disability Status Scale (EDSS) score of 1.5 (IQR: 0.0-2.0). Treatment persistence never dropped below 50% for rituximab, while median persistence was 35.6 months for natalizumab (95% confidence interval (CI): 28.8-44.9), 34.7 for dimethyl fumarate (95% CI: 21.7-56.9), 32.0 for fingolimod (95% CI: 21.1-48.1) and 17.6 for injectables (95% CI: 14.4-20.8). Compared to injectables, adjusted hazard ratios (HRs) for discontinuation were significantly lower for rituximab (0.09; 95% CI: 0.07-0.12), natalizumab (0.39; 95% CI: 0.31-0.48), fingolimod (0.41; 95% CI: 0.30-0.55) and dimethyl fumarate (0.49; 95% CI: 0.36-0.68). Rituximab displayed the highest treatment persistence, supporting B-cell depletion as a first-line option in PoMS.
To characterise age-related changes in sleep macroarchitecture, consolidation and fragmentation across childhood and adolescence in a large real-world paediatric clinical polysomnography cohort, and to examine their relationship with respiratory disturbance severity. We performed a retrospective observational analysis of 419 polysomnographies from children aged 1-18 years at a tertiary sleep unit between January 2023 and December 2024. Participants were categorised as toddlers, pre-schoolers, school-aged children and adolescents. Sleep macroarchitecture, consolidation and fragmentation parameters were scored according to paediatric American Academy of Sleep Medicine criteria. Multivariate general linear models assessed age-group differences, with additional adjustment for apnoea-hypopnoea index and Bonferroni post-hoc testing. Total sleep time decreased with age, while sleep onset and rapid eye movement sleep latencies increased during adolescence. Sleep architecture showed a developmental shift, mainly characterised by increasing Stage N2 and decreasing rapid eye movement sleep proportions, with less robust changes in Stage N3. Fragmentation indices, including arousal index, were higher in adolescents. After adjustment for apnoea-hypopnoea index, age group remained an independent predictor of macroarchitecture, consolidation and fragmentation, whereas respiratory severity was mainly associated with micro-fragmentation indices. Sleep macroarchitecture continues to mature throughout childhood and adolescence, with adolescents frequently exhibiting adult-like sleep patterns largely independent of respiratory disturbance severity. Age-related changes in sleep macroarchitecture and fragmentation provide physiological context for interpreting paediatric polysomnography, particularly near the transition between paediatric and adult scoring frameworks.
Climate change is accelerating toward and beyond critical warming thresholds, with profound implications for ecosystems and human health. Major uncertainties arise from socioeconomic and political responses, while the transgression of Earth-system tipping points may trigger abrupt and irreversible climate dynamics. Climate-related health risks are mediated by direct and indirect exposures, disproportionately affecting vulnerable populations. Children with neurological and neurodevelopmental disorders exhibit heightened susceptibility due to biological, environmental, and disease-specific vulnerabilities, alongside the cumulative lifetime burden of extreme climate events. At the same time, healthcare systems contribute substantially to global greenhouse gas emissions, underscoring the need for climate-responsible clinical practice. Addressing knowledge and training gaps among clinicians is essential. Current initiatives within the European Pediatric Neurology Society highlight advocacy, sustainability actions, and the urgent need for high-quality evidence on climate impacts on brain health across the life span.
Cardiac complications are among the most common causes of death in patients after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying young patients at risk are not established. Cardiovascular magnetic resonance (CMR) imaging with native T1 mapping allows detection of diffuse myocardial alterations but is not routinely available for cardiovascular screening. Whether abnormalities detected by echocardiography reflect underlying myocardial structural changes remains unclear. Pediatric KTx recipients underwent comprehensive transthoracic echocardiography and CMR imaging with native T1 mapping. Associations between echocardiographic measures and T1 values were analyzed using multivariable linear regressions. Receiver operating characteristics analyses assessed the ability of septal E/e' to identify elevated T1 values, with area under the curve (AUC) and optimal cut-offs determined using positive likelihood ratios (LR +). Forty-six pediatric KTx recipients (16 ± 3.5 years old; time since KTx 7.9 ± 5.3 years) were included. Diastolic echocardiographic abnormalities were common, with 87% exhibiting at least one abnormal diastolic parameter. Septal T1 was associated with septal E/e', A-wave, and pulmonary venous atrial reversal, while lateral T1 was associated only with septal E/e'. Optimal septal E/e' cut-offs were 10.550 for detecting an elevated septal T1 (LR +  = 7.143) and 10.630 for detecting an elevated lateral T1 (LR +  = 9). Pediatric KTx recipients with structural myocardial alterations on CMR imaging exhibit detectable abnormalities in routine echocardiographic diastolic parameters. Especially a markedly elevated septal E/e' could identify patients at increased risk for underlying myocardial involvement and justify the use of CMR imaging in post-transplant follow-up.
Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease with diverse phenotypes. We describe the genetics, phenotypes, and treatment of n = 48 DADA2 patients from Germany, Austria, and Switzerland. We report a high incidence of hematological (83%) and immunological features (85%), a comparatively low anti-tumor necrosis factor full-response rate (58%), and a high decision probability (21%) for hematopoietic cell transplantation (HCT). We establish a correlation between genetic variant ADA2 activity and patient ADA2 activity. Remarkably, lower patient ADA2 activity is predictive of neutropenia and shows a trend toward HCT decision, whereas higher patient ADA2 activity is predictive of vasculitis symptoms. Genetic variants with low residual ADA2 activity are significantly more common among patients receiving HCT. Our study corroborates previous observations connecting ADA2 activity and clinical phenotype, which up to now have been mainly based on in vitro data.
We investigated the impact of executive functions (EFs) on academic achievement in a quasi-experimental sample of 56 children born preterm (28-34 weeks' gestation; ages 7-9), without neurological impairment, in favorable educational and socioeconomic environments. Using standardized performance-based tests and daily-life proxy reports, we assessed EFs (inhibition, working memory, flexibility, planning) and academic achievement (reading, spelling, mathematics). Children with EF deficits faced a higher risk of academic difficulties (OR 7.87; 95% CI 2.2-35.2), with planning emerging as the most important predictor. A structured, multifaceted assessment of academic achievement and EFs should be systematically included in follow-up.
Arginase 1 deficiency (ARG1-D) is an ultra-rare urea cycle disorder characterized by progressive spastic paraplegia, developmental delay, epilepsy, and episodic hyperammonemia. Evidence on prevalence and clinical presentation is scarce. Therefore, epidemiology and the phenotypical spectrum were assessed in Germany, Austria, and Switzerland (DACH region). We conducted a questionnaire-based, cross-sectional study of confirmed ARG1-D patients in the DACH region. Patients were stratified into early-diagnosed (newborn screening [NBS] or high-risk family screening [HR]) and diagnosed after symptom onset. We evaluated clinical, biochemical, and therapeutic characteristics of individuals with confirmed ARG1-D. Epidemiological prevalence estimates were derived using national population data. A total of 20 patients were identified (Germany: 12, Austria: 7, Switzerland: 1). Eight were diagnosed early (NBS: 4, HR: 4) and 12 after symptom onset. Symptomatically diagnosed patients (median age 11 years) presented with a broad range of clinical manifestations, specifically progressive spastic paraplegia (67%), epilepsy (58%), dystonia (46%), developmental delay (58%), and hepatopathy (50%). Median age at diagnosis was 35 months in symptomatic patients versus 1 month in early-diagnosed patients (p = 0.03). Estimated pediatric prevalence was 1:1042080 in the DACH region, with high regional differences. Hyperammonemia was reported in 72%. Enzyme therapy had been initiated in 21%; 2 patients underwent liver transplantation. ARG1-D is a rare disease with a prevalence of approximately 1:1000000 individuals, and a complex and progressive clinical phenotype. Detection via NBS or HR allows early diagnosis and treatment initiation, potentially altering the clinical outcome.
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Effective sick-day management, including ketosis home management aimed at preventing diabetic ketoacidosis (DKA), is essential for families living with a child/adolescent with type 1 diabetes (T1D). Adolescents living with T1D and caregivers of younger children living with T1D were invited to participate in an interview consisting of five parts: (I) demographic data, (II) subjective self-ratings on competence in ketosis home management, (III) objective assessment of competence in ketosis home management using a standardized clinical case scenario consisting of 10 management steps, in which participants were asked to describe the actions they would take to prevent DKA, and (IV) practical demonstrations to objectively assess skills in (IVa) urine dipstick self-testing and (IVb) insulin administration, (V) household availability of (Va) urine dipsticks and (Vb) insulin cartridges. (I) We enrolled 61 adolescents and 79 caregivers. (II) Competence in ketosis home management was subjectively self-rated as good to very good. (III) Adolescents reported 4 (median; Q25/Q75 3/5) and caregivers 5 (4/5) of 10 management steps. Never self-testing ketone levels was reported by 33% of adolescents and 11% of caregivers. (IVa) At least one handling error occurred in 100% of adolescents' and in 98% of caregivers' practical demonstrations of urine dipstick self-testing and in (IVb) 98% of adolescents' and 98% of caregivers' insulin administrations. (Va) Altogether urine dipsticks were available in 43% of households, whereas (Vb) insulin cartridges were available in 78% of households. Our results demonstrate a mismatch between challenges in ketosis home management and high subjective self-ratings.
Classic lissencephaly is a malformation of cortical development that includes agyria and pachygyria. The major clinical symptoms are developmental impairment, muscular hypotonia, and drug-resistant epilepsy. The severity of the clinical phenotype depends on the associated gene and mutation. This study aimed to systematically investigate the genotype-specific course of the disease including neurodevelopmental outcome, medical complications, use of non-pharmacological supportive therapies, and its impact on the quality of life of the affected families. 47 patients with genetically and radiologically confirmed lissencephaly were included with mutation in LIS1/PAFAH1B1 (n = 38), DCX (n = 5 males), DYNC1H1 (n = 2), TUBA1A (n = 1) and TUBG1 (n = 1) genes. Standardized questionnaires were completed by families and treating pediatricians. Quality of life was assessed with the PedsQL™ Family Impact Module. Prenatal abnormalities, most commonly microcephaly, were observed in 14/37 (38%) of LIS1/PAFAH1B1 patients and 2/5 (40%) of DCX patients. Early symptoms included microcephaly, developmental delay, muscular hypotonia, and epileptic seizures. The median age at suspected diagnosis was 5 months for LIS1/PAFAH1B1 patients and 9 months for DCX patients. Compared to LIS1/PAFAH1B1, DCX-related lissencephaly patients showed significantly better neurodevelopmental outcome in reaching more advanced milestones such as walking unassisted (z=-2.23, p = 0.026) and speaking sentences (z=-2.53, p = 0.011). Frequent medical complications included recurrent respiratory infections (14/38 (37%) of LIS1/PAFAH1B1 patients; 1/4 (25%) of DCX patients) and dysphagia/ vomiting (23/37 (62%); 2/4 (50%)), which may require tube feeding (15/38 (40%); 1/5 (20%)). A median of eight different supportive therapies was used per patient (range 1-17), with physiotherapy and respiratory therapy considered the most effective. The scores obtained for health-related quality of life (HRQL) were low (parental HRQL mean 61.23; SD 16.79). Our study confirms the severely impaired developmental potential and frequent neurological and medical complications in lissencephaly patients from an early age. The psychomotor prognosis in LIS1/PAFAH1B1-related lissencephaly is significantly worse compared to DCX-related lissencephaly. Supportive therapies are used intensively and are considered to be very effective. The disease puts a high burden on caregivers and the entire family. This emphasizes the need for appropriate epilepsy treatment, personalized care for patients and professional support for their families.
Intracerebral gene therapy is effective for amino acid decarboxylase (AADC) deficiency, but relationships between anatomical putaminal coverage, metabolic dynamics, and clinical recovery remain poorly understood. Assess safety, long-term efficacy, and clinical-radiological correlations in a genetically diverse European cohort of AADC deficiency. Six patients received bilateral intraputaminal rAAV2-hAADC infusion. Motor (GMFM-88), functional (CP-CHILD, Vineland-II), oculogyric crises (OGC), and dyskinesia outcomes were evaluated alongside magnetic resonance imaging (MRI) volumetric coverage and longitudinal 18F-fluorodopa (18F-DOPA) positron emission tomography (PET) parameters. All patients achieved genotype-independent motor improvements and OGC reduction, with no serious adverse events. Clinical recovery did not correlate with the putaminal coverage volume, indicating a biological threshold effect. Transient dyskinesias coincided with an early 18F-DOPA uptake peak (1-3 months post-operative), followed by clinical resolution and sustained activity, reflecting homeostatic synaptic plasticity. Eladocagene exuparvovec offers durable clinical benefits across diverse genotypes. Therapeutic efficacy and the subsequent neuroplasticity sequence seem to depend on reaching a critical threshold of dopamine production rather than on exhaustive anatomical coverage of the putamen. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Effective clinical communication is a core component of patient-centered care. Immersive learning technologies, including virtual patients, virtual reality, and augmented reality, are increasingly used to train clinical communication skills in undergraduate health professions education. However, the existing evidence is fragmented and methodologically heterogeneous. This umbrella review synthesizes review-level evidence on immersive technologies and virtual patients for developing clinical communication skills in undergraduate health professions education and explores barriers to curricular integration and key research gaps. An umbrella review of systematic reviews (with or without meta-analysis) was conducted following PRISMA guidelines. Searches were performed in PubMed, ScienceDirect, CINAHL, and Cochrane Library. Eligible reviews examined immersive technologies (e.g., VR, AR, MR, XR, virtual patients) targeting clinical communication skills in undergraduate learners. Methodological quality was assessed using AMSTAR-2. No pooled meta-analysis was feasible because of substantial heterogeneity in interventions, comparison conditions, and outcome measures. Nine systematic reviews were included. All were rated as critically low in methodological quality, which limits confidence in the conclusions that can be drawn. Across reviews, immersive technologies were reported as potentially beneficial for short-term communication performance, learner engagement, and perceived confidence, particularly in comparison with no intervention or some traditional teaching formats. However, evidence regarding long-term retention, empathy development, non-verbal communication, and transfer to clinical practice remained inconsistent. Substantial heterogeneity in intervention design, outcome measures, and feedback structures limited comparability across reviews.
Neonatal microcytosis may reveal complex hemoglobinopathy combinations requiring molecular clarification. We describe a neonate with homozygous HbE coinherited with α-thalassemia (-3.7 kb deletion) and Hb Constant Spring on the other allele. At birth, marked microcytosis with mild anemia prompted haemoglobin analysis. Despite initial concerns raised by the multiple hemoglobin gene anomalies, follow-up remained asymptomatic, with persistent microcytosis and relative erythrocytosis. Family screening showed that both parents had HbAE. The father carried Hb Constant Spring and the -3.7 deletion, enabling genotype-phenotype correlations. Systematic investigation of neonatal microcytosis can identify rare compound disorders and support tailored follow-up.
Up to 30% of adults with peripheral facial palsy (FP) develop synkinesis, but it's incidence in children remains unclear due to limited long-term data. Children (<18 years) treated for acute peripheral FP at Jena University Hospital between 2009 and 2021 were screened in this cross-sectional study. Bell's palsy and infection-associated FP (e.g., Lyme disease, Zoster) were included, while secondary causes such as tumors, trauma, CNS disorders, and conditions like Guillain-Barré syndrome or Chiari malformation were excluded. Video follow-ups collected clinicodemographic information and PROMs including Facial Clinimetric Evaluation Scale (FaCE), Facial Disability Index (FDI), and Synkinesis Assessment Questionnaire (SAQ). Facial movements were video-recorded and assessed using Sunnybrook and eFACE. Of 85 eligible patients, 26 participated (46% female; response rate 30.6%). Mean age at onset was 8.5 years (range: 0.2-16); 54% had idiopathic FP (IFP) and 46% Lyme-associated FP (LFP). Median follow-up was 7.56 years (range: 2.5-13). All LFP participants and 11 out of 14 IFP participants achieved complete or near-complete recovery (eFACE and Sunnybrook scores 90-100). Four participants (28.6%), exclusively from the IFP group, developed synkinesis, three with functional impairments in PROMs and video-based assessment. Seven participants (five (35.7%) from the IFP group and two (16.7%) from the LFP group) reported that they still experience mental health-related effects of FP today. The data indicate that a relevant proportion (around 21.4%) of children with Bell's palsy develop moderate to severe synkinesis. Long-term follow-up and further research on corticosteroids use in pediatric FP are warranted.
There are still some gaps in understanding the role of inflammation in focal lesional epilepsy. Surgical specimens often contain activated leukocytes, usually thought to originate from the systemic circulation. However, the cerebrospinal fluid, meninges, and skull form a distinct brain-specific immune hub that also reacts to local signals. This study assessed immune hub activation adjacent to epileptogenic lesions in children with focal lesional epilepsy using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET. Children with focal lesional epilepsy who underwent brain FDG-PET for presurgical assessment were compared to age- and sex-matched controls who had total-body FDG-PET for other clinical indications. Spherical regions of interest (ROIs) were placed on the skull, with a cubic ROI on the pons used as a reference. In epilepsy patients, skull ROIs were positioned adjacent to the perilesional hypometabolic defect and contralaterally. In non-epilepsy patients, ROIs mirrored those of epilepsy patients. Metabolic activity was measured as maximum and mean standardized uptake values (SUVmax and SUVmean). Corrected SUV (cSUV), normalized to the pons, and asymmetry index (AI), comparing lesional and contralateral ROIs, were calculated. Twenty-nine epilepsy and 29 non-epilepsy patients (16 boys, 55%) were included. The median age at the time of the scan was 9.0 years (interquartile range, IQR: 3.0-14.0). Across all patients, the median cSUVmax and cSUVmean were 0.36 (IQR: 0.27-0.48) and 0.23 (IQR: 0.16-0.32), respectively. In epilepsy patients, cSUVmax and cSUVmean were 0.33 (IQR: 0.26-0.40) and 0.23 (IQR: 0.18-0.31), and in non-epilepsy patients, 0.44 (IQR: 0.29-0.55) and 0.23 (IQR: 0.13-0.33). Neither cSUVmax nor cSUVmean differed by side (W = 800, P: 0.84; W = 682, P: 0.25), confirming comparability. However, in epilepsy patients, both cSUVmax and cSUVmean were higher on the lesional side than on the contralateral side (W = 43 and W = 49, P < 0.001 for both). In non-epilepsy patients, mirrored ROIs showed no significant difference (W = 142, P: 0.17; W = 154, P: 0.27). AI values for SUVmax and SUVmean were higher in epilepsy than in non-epilepsy patients (t = -4.36 and t = -3.58, both P < 0.001), a difference that remained significant after covariate adjustment, demonstrating metabolic asymmetry relative to the epileptogenic lesion. In children with focal lesional epilepsy, we observed increased metabolic activity in the brain-specific immune hub adjacent to the epileptogenic lesion. This local immune activation likely plays a role in the disease mechanism, which may clarify why immune-modulating treatments can be effective and point the way towards new therapeutic approaches.